9-[2-(2-hydroxyethylamino)-ethylamino]-2-methoxyacridine and method for its production



Patented Nov. 21, 1950 w en a UNITED STATES PATENT OFFICE 2,531,012

' 9-[2- (2' HYnRoxYE'rHYLAMINm-ETHYL- AMINO], 2 METHOXYACRIDINE AND METHOD FOR l'rs PRODUCTION Alexander R. Surrey, Albany, N. Y., assignor to Sterling Drug Inc., Wilmington, Del., a corporation of Delaware No Drawing. Application January 22, 1949, Serial No. 72,268

3 Claims. (Cl. 260279) IIIHCHaUHaNHCHzCHzOH can be prepared by various methods. However,

the procedure preferred in practicing the invention involves heating a mixture of phenol and 9-ch1oro-2-methoxyacridine to form 9-phenoxy- -methoxyacridine hydrochloride (which need not be isolated), which is then heated with 2-(2- hydroxyethylamino) ethylamine. While the foregoing procedure is preferred in practicing my invention, other methods of preparing said basic acridine compound are operable. For example, 9-ch1oro-2-methoxyacridine can be heated directly with 2-(2-hydroxyethylamino) ethylamine without first reacting the former with phenol. In addition, the basic side chain can be attached stepwise to the acridine nucleus. In such a process, 9-chloro2-methoxyacridine or 9-phenoxy-2-methcxyacridine hydrochloride is heated with Z-hydroxyethylamine to give 9-(2-hydroxyethylamino)-2-methoxyacridine, which is then treated with a halogenating agent such as thionyl chloride to yield 9-(2-chloro-ethylamino) -2-methoxyacridine, which, in turn, is treated with 2-hydroxyethylamine to give the desired basic acridine compound, 9-(2-(2-hydroxyethylamino) ethylamino) -2-methoxyacridine.

The salts of the instant invention are prepared by treating the foregoing described basic acridine compound with the appropriate acid. In practicing my invention I found it convenient to employ the dihydrochloride salt. However, other salts are within the scope of the invention. Included among other salts which may be employed are the following, formed by reacting the base with the appropriate relatively non-toxic inorganic or organic acid: the dihydrobromide, diphosphate, disulfate, disulfamate, diethanesulfonate, ditartrate, dicitrate, disuccinate, diacetate, dibenzoate, dloleet and the like.

The following example will further illustrate a specific embodiment of my invention.

9 -(2 -(2 hydroxyethylamino) ethylamino) -2- methoxyacridine dihydrochloride.-A stirred mixture of 50 g. of phenol and 11.5 g. of 9-chloro- -methoxyacridine was heated on the steam bath for about 15 minutes and 6 g. 'of 2-(2-hydroxyethylamino)ethylamine was added. After heating for about 2 hours on the steam bath the slightly cooled reaction mixture was poured into a stirred solution of 12 cc. of cone. hydrochloric acid in cc. of acetone. After about 1 hour the product was filtered off, washed with acetone and then freed from most of the adhering phenol by stirring in hot acetone and filtering the mixture while hot. The resulting solid was recrystallized twice from water-ethanol, yielding about 9.5 g. of the desired product, 9-(2-(2- hydroxyethylamino) ethylamino) -2-methoxyacridine dihydrochloride, M. P. 212-214.5 C. (corn).

1. A compound selected from the group consisting of 9-(2-(2-hydroxyethylamino) ethylamino) -2-methoxyacridine having the formula NHCHzCHzNHCHzCHzOH CHaO and acid addition salts thereof.

2. 9- (2- (2-hydroxyethylamino) ethylamino) -2- methoxyacridine dihydrochloride having the formula Nncmonmnomomon-znoi OHaO 3. In the process of preparing 9-(2-(2- hydroxyethylamino) ethylamino) -2-methoxyacridine having the formula NHOHQCHZNHGHgOHiOH amine.

ALEXANDER R. SURREY.

(References on following page) 2,531,012 3 4 REFERENCES CITED OTHER REFERENCES The following references are of record in the Shrimer et a1., Synthetic-1 Antimalarials, (published in Blodmington, Indiana, 1941), page file of this patent: 30

UNITED STATES PATENTS 5 Mosher, Antimalarials, Natural and Syn- Number N m Date thetic (Edwards Br0s., Ann Arbor, Mich. 1942),

2,113,357 Mietzsch et a1. Apr.. 1938 page 9.

Chem. Abst., v01. 37, page 2408 (1943), (Giting:

Proc. Soc. Exptl. Biol. Med., vol. 52, pages 90-91 (1943).

"Certificate of Correction Patent No. 2,531,012 November 21, 1950 ALEXANDER R. SURREY It is hereby certified that error appears in the printed specification of the above numbered patent requiring correetlon as follows:

Column 1, lines 16 to 19, inclusive, for that portion of the formula reading I 9 II 9 read and that the said Letters Patent should be read as corrected above, so that the same may conform to the record of the case in the Patent Office. Signed and sealed this 23rd day of January, A. D. 1951.

THOMAS F. MURPHY,

Assistant Uommz'ssz'oner of Patents. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF 9-(2-(2-HYDROXYETHYLAMINO) ETHYLAMINO) -2-METHOXYACRIDINE HAVING THE FORMULA 